Treatment of early caries lesions using biomimetic self-assembling peptides – a clinical safety trial

Objective We previously reported that a rationally designed biomimetic self-assembling peptide, P11-4, nucleated hydroxyapatite de novo and was apparently capable of in situ enamel regeneration following infiltration into caries-like lesions. Our present aim was to determine the safety and potential clinical efficacy of a single application of P11-4 on early enamel lesions.Materials and methods Fifteen healthy adults with Class V 'white spot' lesions received a single application of P11-4. Adverse events and lesion appearances were recorded over 180 days.Results Patients treated with P11-4 experienced a total of 11 adverse events during the study, of which two were possibly related to the protocol. Efficacy evaluation suggested that treatment with P11-4 significantly decreased lesion size (p = 0.02) after 30 days and shifted the apparent progression of the lesions from 'arrested/progressing' to 'remineralising' (p <0.001). A highly significant improvement in the global impression of change was recorded at day 30 compared with baseline (p <0.001).Conclusions The results suggest that treatment of early caries lesions with P11-4 is safe, and that a single application is associated with significant enamel regeneration, presumably by promoting mineral deposition within the subsurface tissue

Appropriate use criteria for transesophageal echocardiography in Greece: A single center experience

Introduction The American College of Cardiology Foundation (ACCF) along with the American Society of Echocardiography (ASE) have enabled an accurate and clinically oriented evaluation of echocardiography indications by introducing Appropriate Use Criteria (AUC). Aim This study was designed to evaluate the degree of implementation of AUC for transesophageal echocardiography (TEE) during daily clinical practice in a tertiary university hospital in Greece during the era of economic recession. Materials and Methods From November 2014 to May 2014, we prospectively enrolled 300 patients who were examined in the Echocardiography Laboratory of the First University Cardiology. We recorded the participants' demographic and clinical characteristics using questionnaires and followed a scoring process according to ACCF guidelines to classify patients into an appropriate, inappropriate or uncertain category. The primary endpoint was to assess the association between the class of appropriateness and abnormal TEE results. Results In 89.4% of patients labelled appropriate, TEE was abnormal and significantly higher compared to patients of uncertain eligibility (50%) and to patients for whom TEE was considered to be inappropriate (35%) (p < 0.001). Subgroup analysis revealed a positive association between AUC and an increased possibility for abnormal TEE in female subjects (p = 0.001) as well as in patients who were younger than 50 years old (p < 0.001). A significant association was finally established between AUC and abnormal findings in TEE in patients with no risk factors (p = 0.028) and in patients with more than 3 risk factors (p = 0.013). Conclusion TEE constitutes a medical practice with an optimal cost/effectiveness ratio and should be further encouraged in our country in accordance with the austerity policy as long as the AUC are generally applied

A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation

Nanoparticles introduced in living cells are capable of strongly promoting the aggregation of peptides and proteins. We use here molecular dynamics simulations to characterise in detail the process by which nanoparticle surfaces catalyse the self- assembly of peptides into fibrillar structures. The simulation of a system of hundreds of peptides over the millisecond timescale enables us to show that the mechanism of aggregation involves a first phase in which small structurally disordered oligomers assemble onto the nanoparticle and a second phase in which they evolve into highly ordered beta-sheets as their size increases

Feasibility of real-time three-dimensional stress echocardiography: pharmacological and semi-supine exercise

<p>Abstract</p> <p>Background</p> <p>Real time three dimensional (RT3D) echocardiography is an accurate and reproducible method for assessing left ventricular shape and function.</p> <p>Aim</p> <p>assess the feasibility and reproducibility of RT3D stress echocardiography (SE) (exercise and pharmacological) in the evaluation of left ventricular function compared to 2D.</p> <p>Methods and results</p> <p>One hundred eleven patients with known or suspected coronary artery disease underwent 2D and RT3DSE. The agreement in WMSI, EDV, ESV measurements was made off-line.</p> <p>The feasibility of RT-3DSE was 67%. The inter-observer variability for WMSI by RT3D echo was higher during exercise and with suboptimal quality images (good: k = 0.88; bad: k = 0.69); and with high heart rate both for pharmacological (HR < 100 bpm, k = 0.83; HR ≥ 100 bpm, k = 0.49) and exercise SE (HR < 120 bpm, k = 0.88; HR ≥ 120 bpm, k = 0.78). The RT3D reproducibility was high for ESV volumes (0.3 ± 14 ml; CI 95%: -27 to 27 ml; p = n.s.).</p> <p>Conclusions</p> <p>RT3DSE is more vulnerable than 2D due to tachycardia, signal quality, patient decubitus and suboptimal resting image quality, making exercise RT3DSE less attractive than pharmacological stress.</p

Quantitative analysis of left atrial function in asymptomatic patients with b-thalassemia major using real-time three-dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>There is strong evidence that left atrial (LA) size is a prognostic marker in a variety of heart diseases. Recently, real-time three-dimensional echocardiography (RT3DE) has been reported as a useful tool for studying the phasic changes of the left atrial volumes. The aim of this study was to investigate the performance of the left atrium in beta-thalassemic patients with preserved left ventricular ejection fraction (EF) and no iron overload, using RT3DE.</p> <p>Methods</p> <p>Twenty-eight asymptomatic b-thalassemic patients (32.2 ± 4.3 years old, 17 men) who were on iron chelating therapy, as well as 20 age- and sex-matched healthy controls underwent transthoracic RT3DE. The patient group had normal echocardiographic systolic and diastolic indices, while there was no myocardial iron disposition according to MRI. Apical full volume data sets were obtained and LA volumes were measured at 3 time points of the cardiac cycle: (1) maximum volume (LAmax) at end-systole, just before mitral valve opening; (2) minimum volume (LAmin) at end-diastole, just before mitral valve closure; and (3) volume before atrial active contraction (LApreA) obtained from the last frame before mitral valve reopening or at time of the P wave on the surface electrocardiogram. From the derived values, left atrial active and passive emptying volumes, as well as the respective emptying fractions were calculated.</p> <p>Results</p> <p>Left ventricular EF (59.2 ± 2.5% patients vs. 60.1 ± 2.1% controls), E/A, E/E' were similar between the two groups. Differences in the LAmax, LAmin and LApreA between b-thalassemic patients and controls were non-significant, LAmax:(35.5 ± 13.4 vs 31.8 ± 9.8)cm³, LAmin:(16.0 ± 6.0 vs. 13.5 ±4.2)cm³, and LApreA:(25.4 ± 9.8 vs. 24.3 ± 7.2)cm³. However, left atrial active emptying fraction was reduced in the patient group as compared to the healthy population (34.3 ± 16.4% vs. 43.2 ± 11.4%, p < 0.05).</p> <p>Conclusion</p> <p>RT3DE may be a novel technique for the evaluation of LA function in asymptomatic patients with b-Thalassemia Major. Among three-dimensional volumes and indices, left atrial active emptying fraction may be an early index of LA dysfunction in the specific patient population.</p

Novel Interactions between Actin and the Proteasome Revealed by Complex Haploinsufficiency

Saccharomyces cerevisiae has been a powerful model for uncovering the landscape of binary gene interactions through whole-genome screening. Complex heterozygous interactions are potentially important to human genetic disease as loss-of-function alleles are common in human genomes. We have been using complex haploinsufficiency (CHI) screening with the actin gene to identify genes related to actin function and as a model to determine the prevalence of CHI interactions in eukaryotic genomes. Previous CHI screening between actin and null alleles for non-essential genes uncovered ∼240 deleterious CHI interactions. In this report, we have extended CHI screening to null alleles for essential genes by mating a query strain to sporulations of heterozygous knock-out strains. Using an act1Δ query, knock-outs of 60 essential genes were found to be CHI with actin. Enriched in this collection were functional categories found in the previous screen against non-essential genes, including genes involved in cytoskeleton function and chaperone complexes that fold actin and tubulin. Novel to this screen was the identification of genes for components of the TFIID transcription complex and for the proteasome. We investigated a potential role for the proteasome in regulating the actin cytoskeleton and found that the proteasome physically associates with actin filaments in vitro and that some conditional mutations in proteasome genes have gross defects in actin organization. Whole-genome screening with actin as a query has confirmed that CHI interactions are important phenotypic drivers. Furthermore, CHI screening is another genetic tool to uncover novel functional connections. Here we report a previously unappreciated role for the proteasome in affecting actin organization and function

Successful management of multiple permanent pacemaker complications – infection, 13 year old silent lead perforation and exteriorisation following failed percutaneous extraction, superior vena cava obstruction, tricuspid valve endocarditis, pulmonary embolism and prosthetic tricuspid valve thrombosis

A 59 year old man underwent mechanical tricuspid valve replacement and removal of pacemaker generator along with 4 pacemaker leads for pacemaker endocarditis and superior vena cava obstruction after an earlier percutaneous extraction had to be abandoned, 13 years ago, due to cardiac arrest, accompanied by silent, unsuspected right atrial perforation and exteriorisation of lead. Postoperative course was complicated by tricuspid valve thrombosis and secondary pulmonary embolism requiring TPA thrombolysis which was instantly successful. A review of literature of pacemaker endocarditis and tricuspid thrombosis along with the relevant management strategies is presented. We believe this case report is unusual on account of non operative management of right atrial lead perforation following an unsuccessful attempt at percutaneous removal of right sided infected pacemaker leads and the incidental discovery of the perforated lead 13 years later at sternotomy, presentation of pacemaker endocarditis with a massive load of vegetations along the entire pacemaker lead tract in superior vena cava, right atrial endocardium, tricuspid valve and right ventricular endocardium, leading to a functional and structural SVC obstruction, requirement of an unusually large dose of warfarin postoperatively occasioned, in all probability, by antibiotic drug interactions, presentation of tricuspid prosthetic valve thrombosis uniquely as vasovagal syncope and isolated hypoxia and near instantaneous resolution of tricuspid prosthetic valve thrombosis with Alteplase thrombolysis

Circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells and arterial function in patients with beta-thalassaemia major

Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133+VEGFR2+ and CD34+VEGFR2+ cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133+VEGFR2+ and CD34+VEGFR2+ cells